This invention relates to methods for the diagnosis of gastrointestinal disorders in humans and other animals.
Factors adversely affecting the function of the gastrointestinal system in humans are exceedingly varied in their nature. Such disorders may arise in the upper or lower gastrointestinal tracts or both. There is a broad range of causes of gastrointestinal disorders, including genetic, physiological, environmental, and psychogenic factors. Accordingly, the diagnosis and management of these disorders can be exceptionally difficult. A detailed discussion of gastrointestinal tract functions, disorders, causes, and treatments can be found in Spiro, Clinical Gastroenterology (3d. edition 1983).
Among the chronic disorders of the upper gastrointestinal tract are those which fall under the general categories of gastritis and peptic ulcer disease. (The upper gastrointestinal tract is generally defined as including the esophagus, the stomach, the duodenum, the jejunum, and ileum.) Peptic ulcers are lesions of the gastrointestinal tract lining, characterized by loss of tissue due to the action of digestive acids and pepsin. It has been generally held that peptic ulcers are caused by gastric hypersecretion, decreased resistance of the gastric lining to digestive acids and pepsin or both. Gastritis is, by definition, an inflammation of the stomach mucosa. In practice, though, the disorder is manifested by a broad range of poorly-defined, and heretofore inadequately treated, symptoms such as indigestion, "heart burn", dyspepsia and excessive eructation. A general discussion of gastritis appears in B. J. Marshall and J. R. Warren, "Unidentified Curved Bacilli in the Stomach of Patients with Gastritis and Peptic Ulceration", The Lancet, 1311-1315 (1984), and in R. Greenlaw, et al., "Gastroduodenitis, A Broader Concept of Peptic Ulcer Disease", 25 Digestive Diseases and Sciences 660-672 (1980).
As with the management of any disorder, the rapid, precise, and accurate diagnosis of gastrointestinal disorders is of paramount importance. The typical means used to diagnose the gastrointestinal disorder presented by a given patient will depend upon such factors as the nature and severity of symptoms, the overall health of the individual, the medical history of the patient, the need for a specific diagnosis in order to implement a treatment with reasonable likelihood of success, and the availability of diagnostic devices. However, the diagnostic methods typically employed in the art are often slow, cumbersome, costly and may yield equivocal or inaccurate results. See, e.g., Spiro, supra. Thus, for patients not having severe symptoms, a precise diagnosis of a gastrointestinal disorder might not be attempted. Such patients may simply be treated with conventional therapies, such as with antacids or drugs which inhibit stomach acid secretion. While such therapies might provide temporal symptomatic relief, a "cure" is often not effected. See, for example, A. J. McLean, et al., "Cytoprotective Agents and Ulcer Relapse", 142 The Medical Journal of Australia, Special Supplement, S25-S28 (1985), and O. Nyren, et al., "Absence of Therapeutic Benefit from Antacids or Cimetidine in Non-ulcer Dyspepsia" 314 New England Journal of Medicine 339-343 (1986). More effective treatments may depend upon better diagnoses of the actual underlying gastrointestinal disorder. In particular, it has been discovered that many such gastrointestinal disorders are mediated by infection of gastric mucosa by bacteria. See, B. J. Marshall, et al, "Pyloric Campylobacter Infection and Gastroduodenal Disease," the Medical Journal of Australia, 439-444 (1985). Thus, treatment of the bacterial infection may be required in order to effectively treat the manifested gastrointestinal disorder.
Accordingly, a simple diagnostic test for gastrointestinal disorders could afford substantial advantages in the proper and effective treatment of patients having gastrointestinal disorders. Such a test should be easily performed, allowing definitive interpretation, and yield a result with a high degree of correlation to the presence or absence of the gastrointestinal disorder. A blood serum test for gastritis is suggested, for example, in B. J. Marshall, et al., "Pyloric Campylobacter Serology", 2, The Lancet, 1442 (1985). A blood serum test for pepsinogen is described in I. M. Samloff, et al., "Relationships Among Serum Pepsinogen I, Serum Pepsinogen II and Gastric Mucosal Histology" 83 Gastroenterology 204-209 (1982). A non-invasive test for gastric acid activity is described in U.S. Pat. No. 4,548,805, Sack, et al., issued Oct. 22, 1985.
It has now been discovered that gastrointestinal disorders of the upper gastrointestinal tract may be detected and diagnosed by methods involving the administration to a human or lower animal subject of urea followed by analyzing the breath of the subject to detect the presence of products of urea hydrolysis. The methods of this invention thus provide a rapid, inexpensive, non-invasive and accurate diagnosis of such gastrointestinal disorders.